Payload Release Profile and Anti-Cancer Stem Cell Properties of Compositionally Different Polymeric Nanoparticles Containing a Copper(II) Complex
journal contributionposted on 2023-05-25, 09:43 authored by G Passeri, J Northcote-Smith, K Suntharalingam
Cancer stem cells (CSCs) are linked to tumour relapse and metastasis, the main reason for cancer-related deaths. The application of polymeric nanoparticles as drug delivery systems to target CSCs is relatively unexplored. Here, we report the encapsulation of a CSC-potent copper(II) complex 1 by two compositionally different methoxy poly(ethylene glycol)-b-poly(D,L-lactic-co-glycolic) acid (PEG–PLGA) copolymers. Specifically, we used PEG–PLGA (5000:10,000 Da, 1:1 LA:GA) and PEG–PLGA (5000:10,000 Da, 4:1 LA:GA) polymers to prepare spherical nanoparticle formulations 1:1 NP15 and 4:1 NP15, respectively, both with a 15% feed of 1. The two formulations show distinct biophysical and in vitro properties. For example, (i) 4:1 NP15 displays a slower payload release profile than 1:1 NP15 in physiologically relevant solutions, (ii) 4:1 NP15 exhibits statistically greater potency towards breast CSCs than bulk breast cancer cells grown in monolayers, whereas 1:1 NP15 is equally potent towards breast CSCs and bulk breast cancer cells, and (iii) 4:1 NP15 shows significantly greater potency towards three-dimensionally cultured mammospheres than 1:1 NP15. This study shows that the release profile and anti-breast CSC properties of PEG–PLGA nanoparticle formulations (containing 1) can be perturbed (and possibly controlled) by modifying the proportion of glycolic acid within the PLGA component.
Author affiliationDepartment of Chemistry, University of Leicester
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